Both sides find themselves near the bottom of the table, but Samp face the risk of being cut adrift in the bottom three.
Match preview
Empoli come into the weekend just four places above their upcoming opponents, but they are 10 points clear of them, so a relegation battle is not on the agenda for them currently.
Given their form too, it is unlikely they will be dragged into any scrap at the bottom either, as a gradual rise into mid-table looks likely thanks to their recent results.
Only runaway league-leaders Napoli have beaten Empoli in their last five matches, and only one side outside the top seven have beaten them all season - Spezia on the opening day.
Paolo Zanetti's side earned a dramatic point in the capital last time out against Lazio, when Francesco Caputo and Razvan Marin goals in the final five minutes brought them back from the dead after being 2-0 down.
They simply have not scored enough goals overall this season though, as teenager Tommaso Baldanzi is their top scorer with just three, and only Samp and Cremonese have scored fewer.
The re-signing of Caputo from their next opponents should add the firepower they need though, as the 35-year-old scored 43 league goals in two seasons at the club between 2017 and 2019, and he is already off the mark.
An emotional week for Sampdoria which saw them lose one of the club's biggest icons, Gianluca Vialli, also saw them struggle on the field too.
They lost to Napoli in the league before being knocked out of the Coppa Italia by Fiorentina in midweek.
That leaves them fighting on just the league front now, and they have one hell of a challenge to get out of the current predicament they find themselves in.
Sitting 18th after 17 games with just nine points represents their worst-ever start to any Serie A season, as well as being the only club still in single digits for goals scored in the division.
They have scored just eight this season from six different players, as Manolo Gabbiadini and Filip Djuricic sit as their top scorers with a paltry two.
It also does not help their cause that going into the weekend, no side had conceded as many goals.
A win at Sassuolo was huge on their return to action at the start of the month, and it showed the benefits of being on their game and aggressive from the start.
They found themselves 2-0 up after just half an hour, and despite all of Sassuolo's dominance after that, they could not peg Samp back.
They are the only goals they have scored in their last seven games though, with the other six unsurprisingly all ending in defeat.
Some positive omens for Dejan Stankovic's men is that they have won on their last three trips to Empoli, and seven of their nine points this season have come on the road.
Empoli Serie A form:
L
W
L
W
D
D
Sampdoria Serie A form:
L
L
L
L
W
L
Sampdoria form (all competitions):
L
L
L
W
L
L
Team News
Mattia Destro remains out for Empoli in attack, but the recent signing of Caputo will help fill the void in his absence while he recovers from a calf injury.
Another former Samp player who made a recent return to Empoli like Caputo, Lorenzo Tonelli, will not feature here as he continues to nurse a serious knee injury that has kept him out since last season.
Jean-Daniel Akpa Akpro will be available again after he served his one-match suspension following his red card at Udinese.
Jeison Murillo's red card in midweek in Sampdoria's cup exit against Fiorentina will not carry over into the league, so the Colombian defender will still be available for selection here.
Tomas Rincon was dismissed against Napoli in their last league fixture though, so after featuring in the cup, the midfielder will miss this game through suspension.
Abdelhamid Sabiri and Omar Colley could come into the league side after making returns from respective injuries in the cup, but Fabio Quagliarella, Andrea Conti and Ignacio Pussetto are among those still out.
Empoli possible starting lineup:
Vicario; Stojanovic, Ismajli, Luperto, Parisi; Marin, Grassi, Akpa Akpro; Bajrami, Caputo, Satriano
Sampdoria possible starting lineup:
Audero; Murillo, Colley, Nuytinck; Leris, Sabiri, Vieira, Augelio, Djuricic; Lammers, Gabbiadini
We say: Empoli 2-0 Sampdoria
Empoli have found form at a good time and look set to move away from trouble, but their recent poor record against Samp may linger in the memory.